Venkateswaran Vasundara, Haddad Ahmed Q, Fleshner Neil E, Fan Rong, Sugar Linda M, Nam Rob, Klotz Laurence H, Pollak Michael
Division of Urology, S-118B, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Toronto, ON M4N3M5, Canada.
J Natl Cancer Inst. 2007 Dec 5;99(23):1793-800. doi: 10.1093/jnci/djm231. Epub 2007 Nov 27.
Prior research suggested that energy balance and fat intake influence prostate cancer progression, but the influence of dietary carbohydrate on prostate cancer progression has not been well characterized. We hypothesized that hyperinsulinemia resulting from high intake of refined carbohydrates would lead to more rapid growth of tumors in the murine LNCaP xenograft model of prostate cancer.
Athymic mice were injected subcutaneously with LNCaP human prostate cancer cells and, when tumors were palpable, were randomly assigned (n = 20 per group) to high carbohydrate-high fat or low carbohydrate-high fat diets. Body weight and tumor volume were measured weekly. After 9 weeks, serum levels of insulin and insulin-like growth factor 1 (IGF-1) were measured by enzyme immunoassay. AKT activation and the levels of the insulin receptor in tumor cells were determined by immunoblotting. The in vitro growth response of LNCaP cells to serum from mice in the two treatment groups was measured based on tetrazolium compound reduction. All statistical tests were two-sided.
After 9 weeks on the experimental diets, mice on the high carbohydrate-high fat diet were heavier (mean body weight of mice on the high carbohydrate-high fat diet = 34 g versus 29.1 g on the low carbohydrate-high fat diet, difference = 4.9 g, 95% CI = 3.8 to 6.0 g; P = .003), experienced increased tumor growth (mean tumor volume in mice on high carbohydrate-high fat diet = 1695 versus 980 mm3 on low carbohydrate-high fat diet, difference = 715 mm3, 95% CI = 608 to 822 mm3; P<.001), and experienced a statistically significant increase in serum insulin and IGF-1 levels. Tumors from mice on the high carbohydrate-high fat diet had higher levels of activated AKT and modestly higher insulin receptor levels than tumors from mice on the low carbohydrate-high fat diet. Serum from mice on the high carbohydrate-high fat diet was more mitogenic for LNCaP cells in vitro than serum from mice fed the low carbohydrate-high fat diet.
A diet high in refined carbohydrates is associated with increased tumor growth and with activation of signaling pathways distal to the insulin receptor in a murine model of prostate cancer.
先前的研究表明能量平衡和脂肪摄入会影响前列腺癌的进展，但膳食碳水化合物对前列腺癌进展的影响尚未得到充分阐明。我们假设，在前列腺癌的小鼠LNCaP异种移植模型中，高糖饮食导致的高胰岛素血症会使肿瘤生长更快。
将无胸腺小鼠皮下注射LNCaP人前列腺癌细胞，当肿瘤可触及后，将小鼠随机分组（每组n = 20），分别给予高碳水化合物 - 高脂肪或低碳水化合物 - 高脂肪饮食。每周测量体重和肿瘤体积。9周后，通过酶免疫测定法测量血清胰岛素和胰岛素样生长因子1（IGF - 1）水平。通过免疫印迹法测定肿瘤细胞中AKT的激活情况和胰岛素受体水平。基于四氮唑化合物还原法测量LNCaP细胞对两个治疗组小鼠血清的体外生长反应。所有统计检验均为双侧检验。
在实验饮食9周后，高碳水化合物 - 高脂肪饮食组的小鼠体重更重（高碳水化合物 - 高脂肪饮食组小鼠的平均体重 = 34 g，而低碳水化合物 - 高脂肪饮食组为29.1 g，差值 = 4.9 g，95% CI = 3.8至6.0 g；P = 0.003），肿瘤生长加快（高碳水化合物 - 高脂肪饮食组小鼠的平均肿瘤体积 = 1695 mm³，而低碳水化合物 - 高脂肪饮食组为980 mm³，差值 = 715 mm³，95% CI = 608至822 mm³；P < 0.001），血清胰岛素和IGF - 1水平有统计学显著升高。高碳水化合物 - 高脂肪饮食组小鼠的肿瘤中，AKT激活水平更高，胰岛素受体水平略高于低碳水化合物 - 高脂肪饮食组小鼠的肿瘤。高碳水化合物 - 高脂肪饮食组小鼠的血清在体外对LNCaP细胞的促有丝分裂作用比低碳水化合物 - 高脂肪饮食组小鼠的血清更强。
在前列腺癌小鼠模型中，高糖饮食与肿瘤生长增加以及胰岛素受体下游信号通路的激活有关。
